Lead exposure and amyotrophic lateral sclerosis

BACKGROUND: Previous interview-based studies have suggested that exposure to neurotoxicants including metals might be related to ALS. METHODS: We evaluated the relation of lead exposure to ALS, using both biological measures and interviews, in a case-control study conducted in New England from 1993 to 1996. Cases (N = 109) were recruited at two hospitals in Boston, MA. Population controls (N = 256) identified by random-digit dialing were frequency-matched to cases by age, sex, and region of residence within New England. RESULTS: Risk of ALS was associated with self-reported occupational exposure to lead (odds ratio [OR] = 1.9; 95% confidence interval [CI] = 1.1-3.3), with a dose response for lifetime days of lead exposure. Blood and bone lead levels were measured in most cases (N = 107) and in a subset of controls (N = 41). Risk of ALS was associated with elevations in both blood and bone lead levels. ORs were 1.9 (95% CI = 1.4-2.6) for each microg/dl increase in blood lead, 3.6 (95% CI = 0.6-20.6) for each unit increase in log-transformed patella lead, and 2.3 (95% CI = 0.4-14.5) for each unit increase in log-transformed tibia lead. CONCLUSIONS: These results are consistent with previous reports and suggest a potential role for lead exposure in the etiology of ALS.     

Lead levels and ischemic heart disease in a prospective study of middle-aged and elderly men: the VA Normative Aging Study

BACKGROUND: Lead exposure has been associated with higher blood pressure, hypertension, electrocardiogram abnormalities, and increased mortality from circulatory causes. OBJECTIVE: We assessed the association between bone lead-a more accurate biomarker of chronic lead exposure than blood lead-and risk for future ischemic heart disease (IHD). METHODS: In a prospective cohort study (VA Normative Aging Study), 837 men who underwent blood or bone lead measurements at baseline were followed-up for an ischemic heart disease event between 1 September 1991 and 31 December 2001. IHD was defined as either a diagnosis of myocardial infarction or angina pectoris that was confirmed by a cardiologist. Events of fatal myocardial infarction were assessed from death certificates. RESULTS: An IHD event occurred in 83 cases (70 nonfatal and 13 fatal). The mean blood, tibia, and patella lead levels were higher in IHD cases than in noncases. In multivariate Cox-proportional hazards models, one standard deviation increase in blood lead level was associated with a 1.27 (95% confidence interval, 1.01-1.59) fold greater risk for ischemic heart disease. Similarly, a one standard deviation increase in patella and tibia lead levels was associated with greater risk for IHD (hazard ratio for patella lead = 1.29; 95% confidence interval, 1.02-1.62). CONCLUSIONS: Men with increased blood and bone lead levels were at increased risk for future IHD. Although the pathogenesis of IHD is multifactorial, lead exposure may be one of the risk factors.     

Comparability of mortality follow-up before and after the National Death Index

Prior to 1979, epidemiologic studies which included mortality follow-up on large cohorts relied on death certificates from last state of residence and expensive follow-up techniques to determine survival. Beginning with 1979, the National Death Index can be used to search death certificate files from all 50 states, the Virgin Islands, and Puerto Rico. This paper addresses the issue of whether mortality follow-up in epidemiologic studies based on a single state death certificate search using only data available in 1970-1975 can be compared with post-1979 mortality follow-up using the National Death Index. This question was addressed by following a cohort of 2,925 coronary heart disease and cerebrovascular disease 1980 hospital discharges from 1980 through 1983 with the use of both the National Death Index and the Minnesota Death Index (MINNDEX). Algorithms for evaluating potential death certificate matches were developed independently for both systems. The systems agreed on the survival status of 98% of the cohort, and both identified 31% as dead. This study supports the comparison of results of National Death Index follow-up to pre-National Death Index studies using algorithms such as the MINNDEX, and provides evidence that trend analyses relying on single state death searches pre-1979 and on the National Death Index from 1979 are valid, particularly in chronically ill persons.     

Neurodegenerative diseases in welders and other workers exposed to high levels of magnetic fields

BACKGROUND: Previous work has suggested an increase in risk of amyotrophic lateral sclerosis (ALS) and Alzheimer's disease among workers exposed to extremely low-frequency magnetic fields (ELF-MF). We evaluated the relation between ELF-MF from occupational exposures and mortality from neurodegenerative diseases. METHODS: The study was based on a cohort of Swedish engineering industry workers, comprising 537,692 men and 180,529 women. The cohort was matched against the 3 most recent censuses and The Causes of Death Registry. Levels of ELF-MF exposure were obtained by linking occupation according to the censuses to a job exposure matrix. We used 4 levels of exposure and considered both the primary and contributing causes of death, 1985-96. RESULTS: The risk of Alzheimer's disease as primary or contributing cause of death increased with increasing exposure to ELF-MF among both men and women, with a relative risk (RR) of 4.0 and a 95% confidence interval (95% CI) of 1.4-11.7 in the highest exposure group for both sexes combined. There was a RR of 2.2 (95% CI: 1.0-4.7) for ALS in the highest exposure group with the suggestion of an exposure-response relationship. No evidence of increased risk was seen for Parkinson's disease or multiple sclerosis. CONCLUSIONS: The findings support previous observations of an increased risk of Alzheimer's disease and ALS among employees occupationally exposed to ELF-MF. Further studies based on morbidity data are warranted.     

Vitamin E intake and risk of amyotrophic lateral sclerosis: a pooled analysis of data from 5 prospective cohort studies

The authors investigated whether vitamin E intake was associated with amyotrophic lateral sclerosis (ALS) in the Nurses' Health Study (1976-2004), the Health Professionals Follow-up Study (1986-2004), the Cancer Prevention Study II Nutrition Cohort (1992-2004), the Multiethnic Cohort Study (1993-2005), and the National Institutes of Health-AARP Diet and Health Study (1995-2005). ALS deaths were identified through the National Death Index. In the Nurses' Health Study and the Health Professionals Follow-up Study, confirmed nonfatal ALS cases were also included. Cohort-specific results were estimated using Cox proportional hazards models and pooled using random-effects models. Among 1,055,546 participants, 805 developed ALS. Overall, using vitamin E supplements was not associated with ALS. However, within cohorts with information on duration of vitamin E supplement use (231 cases), ALS rates declined with increasing years of use (P-trend=0.01). Compared with nonusers, the multivariable-adjusted relative risk was 1.05 (95% confidence interval (CI): 0.60, 1.84) among users for ≤1 year (12 cases), 0.77 (95% CI: 0.33, 1.77) among users for 2-4 years (7 cases), and 0.64 (95% CI: 0.39, 1.04) among users for ≥5 years (18 cases). For dietary vitamin E intake, the multivariable-adjusted relative risk comparing the highest quartile with the lowest was 0.79 (95% CI: 0.61, 1.03); an inverse dose-response was evident in women (P-trend=0.002) but not in men (P-trend=0.71). In this large, pooled prospective study, long-term vitamin E supplement use was associated with lower ALS rates. A possible protective effect of vitamin E deserves further consideration.     

Amyotrophic lateral sclerosis,lead, and genetic susceptibility: polymorphisms in the delta-aminolevulinic acid dehydratase and vitamin D receptor genes

Previous studies have suggested that lead exposure may be associated with increased risk of amyotrophic lateral sclerosis (ALS). Polymorphisms in the genes for delta-aminolevulinic acid dehydratase (ALAD) and the vitamin D receptor (VDR) may affect susceptibility to lead exposure. We used data from a case-control study conducted in New England from 1993 to 1996 to evaluate the relationship of ALS to polymorphisms in ALAD and VDR and the effect of these polymorphisms on the association of ALS with lead exposure. The ALAD 2 allele (177G to C; K59N) was associated with decreased lead levels in both patella and tibia, although not in blood, and with an imprecise increase in ALS risk [odds ratio (OR) = 1.9; 95% confidence interval (95% CI), 0.60-6.3]. We found a previously unreported polymorphism in ALAD at an Msp1 site in intron 2 (IVS2+299G>A) that was associated with decreased bone lead levels and with an imprecise decrease in ALS risk (OR = 0.35; 95% CI, 0.10-1.2). The VDR B allele was not associated with lead levels or ALS risk. Our ability to observe effects of genotype on associations of ALS with occupational exposure to lead or with blood or bone lead levels was limited. These findings suggest that genetic susceptibility conferred by polymorphisms in ALAD may affect ALS risk, possibly through a mechanism related to internal lead exposure.     

Amosite mesothelioma in a cohort of asbestos workers

A cohort of 820 asbestos workers with a short duration of exposure to amosite between 1941 and 1945 was followed. These men were alive five years after starting work and were observed until 1988. Seventeen cases of malignant mesothelioma (eight pleural, nine peritoneal) were found. The mean age at the onset of exposure was 33 years for men with pleural mesothelioma and 30 years for those with peritoneal mesothelioma. Chest pain was the main symptom in pleural mesothelioma and abdominal pain in peritoneal mesothelioma. Open lung biopsy was the most useful diagnostic approach for pleural mesothelioma, whereas for peritoneal mesothelioma it was exploratory laparotomy. Pleural patients died of pulmonary insufficiency, and peritoneal patients of wasting and inanition. In both groups the death certificate diagnosis was less accurate than the clinical diagnosis at death. The mean survival was 12.5 months from first symptom to death for the pleural group and 5.4 months for the peritoneal group.     

Polycyclic aromatic hydrocarbon-DNA adducts and survival among women with breast cancer

Polycyclic aromatic hydrocarbons (PAH) are mammary carcinogens in animal studies, and a few epidemiologic studies have suggested a link between elevated levels of PAH-DNA adducts and breast cancer incidence. An association between PAH-DNA adducts and survival among breast cancer cases has not been previously reported. We conducted a survival analysis among women with newly diagnosed invasive breast cancer between 1996 and 1997, enrolled in the Long Island Breast Cancer Study Project. DNA was isolated from blood samples that were obtained from cases shortly after diagnosis and assayed for PAH-DNA adducts using ELISA. Among the 722 cases with PAH-DNA adduct measurements, 97 deaths (13.4%) from all causes and 54 deaths (7.5%) due to breast cancer were reported to the National Death Index (NDI) by December 31, 2002. Using Cox proportional hazards models and controlling for age at diagnosis, we did not find evidence that all-cause mortality (hazard ratio (HR)=0.88; 95% confidence interval (CI): 0.57-1.37), or breast cancer mortality (HR=1.20; 95% CI: 0.63-2.28) was strongly associated with detectable PAH-DNA adduct levels compared with non-detectable adducts; additionally, no dose-response association was observed. Among a subgroup with treatment data (n=520), adducts were associated with over a two-fold higher mortality among those receiving radiation, but mortality for adducts was reduced among hormone therapy users. Results from this large population-based study do not provide strong support for an association between detectable PAH-DNA adducts and survival among women with breast cancer, except perhaps among those receiving radiation treatment.     

62例肌萎缩侧索硬化的临床分析

目的探讨肌萎缩侧索硬化(Amyotrophic Lateral Sclerosis,ALS)的临床和电生理特征。方法收集2004年1月1日至2010年6月30日期间佛山市中医院神经内科收治的62例ALS患者,回顾性分析这些病人的资料并总结其临床特征。结果本组病人的主要临床特征为慢性隐袭起病,中老年发病(平均发病年龄为49.3岁),男性多发(男女比例为1.48∶1),首发症状多为单侧上肢肌无力(54.8%),可伴有肌肉萎缩,吞咽、言语困难等,电生理检查均表现为脑神经和多个脊髓节段广泛的神经源性损害。结论肌萎缩侧索硬化症是一种累及脊髓前角细胞、脑干运动神经核及锥体束,具有上下运动神经元损害并存的慢性进行性神经系统变性疾病。早期诊断是本病的难点,且容易出现误诊。肌电图对本病的诊断和鉴别诊断有重要意义。     

Surveillance of mortality among atomic bomb survivors living in the United States using the National Death Index

BACKGROUND: The National Death Index is a useful source to establish the death of an individual and to determine the cause of death. We identified deaths in atomic bomb survivors in the United States who were lost to follow-up through the National Death Index, and examined the completeness of mortality ascertainment in atomic bomb survivors in the US through the National Death Index. METHODS: Since 1977, biennial medical examinations of atomic bomb survivors in the US have been conducted. The 1,073 atomic bomb survivors in the US included 764 individuals who had medical examinations at least once in sixteen years from 1977 through 1993 and 309 individuals who reported atomic bomb survivorship to medical examination project themselves. Of the 1,073 survivors living in the US, 471 people who participated in the ninth health examinations of atomic bomb survivors living in the US in 1993 were removed, and two people among the remaining 602 individuals had no information about their birth dates and Social Security numbers. An investigation of those deceased between 1979 and 1993 was conducted among 600 of the atomic bomb survivors in the US. Death certificates for atomic bomb survivors in the US were requested from the National Death Index. A comparison was made between the information on the death certificates acquired through the National Death Index and the data ascertained from the medical examination project conducted from 1979 through 1993. RESULTS: Forty-nine death certificates were obtained using the National Death Index. By sex, the dominant cause of death in females was malignant neoplasm, accounting for 53%. In males, it was circulatory disease, accounting for 37%. The National Death Index and the medical examination project determined that 57 deaths had occurred between 1979 and 1993. The sensitivity and specificity of the National Death Index is 86% and 97% respectively. CONCLUSION: It is suggested that the National Death Index is useful to follow up mortality among atomic bomb survivors in the US.     

62例肌萎缩侧索硬化的临床分析

目的探讨肌萎缩侧索硬化（Amyotrophic Lateral Sclerosis,ALS）的临床和电生理特征。方法收集2004年1月1日至2010年6月30日期间佛山市中医院神经内科收治的62例ALs患者,回顾性分析这些病人的资料并总结其I临床特征。结果本组病人的主要临床特征为慢性隐袭起病,中老年发病（平均发病年龄为49．3岁）,男性多发（男女比例为1．48：1）．首发症状多为羊侧上肢肌无力（54．8％）,可伴有肌肉萎缩,吞咽、言语困难等,电生理检查均表现为脑神经和多个脊髓节段广泛的神经源性损害。结论肌萎缩侧索硬化症是一种累及脊髓前角细胞、脑干运动神经核及锥体柬,具有上Tig动神经元损害并存的慢性进行性神经系统变性疾病。早期诊断是本病的难点,且容易出现误诊。肌电图对本病的诊断和鉴别诊断有重要意义。     

Risk of mortality related to widowhood in older Mexican Americans

PURPOSE: To examine the risk and correlates of mortality after death of a spouse and whether mortality risk varies by sex. METHODS: Prospective cohort study (1993 to 2000) of 1693 Mexican Americans ages 65 years and older who were married at baseline. Mortality was confirmed by matching records with the National Death Index or through proxy report. Risk of death related to incidence of widowhood was estimated by using proportional hazard regression and adjusted for age, education, US nativity, financial strain, social support, health behaviors, medical conditions, disability, and depressive symptoms. RESULTS: In the unadjusted Cox hazard analysis, widowed men are significantly more likely to die (HR=2.32, CI=1.48 to 3.61), but loss of spouse has no significant effect on the subsequent risk of death for widowed women (HR=1.50, CI=0.90 to 2.49). After adjustment for covariates known to influence survival, the association between widowhood and mortality in men remained significant, but the magnitude of the association decreased by 26%, which suggests a partial mediation effect of these factors on survival. The trajectory of the survival curve shows that the risk of death associated with widowhood is highest within the first 2 years. CONCLUSIONS: Widowhood in older Mexican American men is a risk factor for mortality.     

Onset of symptoms and time to diagnosis of Clostridium difficile-associated disease following discharge from an acute care hospital.

OBJECTIVE: To identify patients with a diagnosis of Clostridium difficile-associated disease (CDAD) in the ambulatory care setting and determine the relationship of symptom onset and diagnosis to prior hospitalization and exposure to antimicrobials. DESIGN: Single-center, retrospective study. METHODS: Medical records were reviewed for outpatients and hospitalized patients with a stool assay positive for C. difficile toxin A from January 1998 through March 2005. Patients with recurrent CDAD or residing in an extended-care facility were excluded. CDAD in patients who had been hospitalized in the 100 days prior to diagnosis was considered potentially hospital-associated. RESULTS: Of the 84 patients who met the inclusion criteria, 75 (89%) received a diagnosis 1-60 days after hospital discharge (median, 12 days), and 71 (85%) received a diagnosis within 30 days after discharge. Of the 69 patients whose records contained information regarding time of symptom onset, 62 (90%) developed diarrhea within 30 days of a previous hospital discharge, including 7 patients with symptom onset prior to discharge and 9 with onset on the day of discharge. The median time from symptom onset to diagnosis was 6 days. Of 84 patients, 77 (92%) had received antimicrobials during a prior hospitalization, but 55 (65%) received antimicrobials both as inpatients and as outpatients. CONCLUSION: If all cases of CDAD diagnosed within 100 days of hospital discharge were assumed to be hospital-associated, 71 (85%) of 84 patients with CDAD were identified within 30 days, and 75 (89%) of 84 were identified by day 60. Continued outpatient antimicrobial exposure confounds determination of whether late-onset cases are community- or hospital-associated.     

发热伴血小板减少综合征确诊病例特征及家庭负担调查分析

目的 了解合肥市发热伴血小板减少综合征（SFTS）实验室确诊病例相关特征和家庭负担,为科学、有效防控提供依据。方法 回顾性分析SFTS确诊病例流行病学调查表和家庭负担调查表。结果 2014—2019年间合肥市133例SFTS确诊病例,实验室检测阳性率43.75%,死亡22例,SFTS病死率16.5%。合肥市有4个县（市）多发,但病死率无统计学意义（〖XC小五号.EPS;P〗=1.230,P=0.312）。75.2%的病例集中在4-7月份。死亡与存活病例平均发病年龄的差异无统计学意义（Z=-1.337,P=0.183）,主要是农民（78.2%）。80.5%的病例发病前一个月居住在丘陵/山区,78.9%的病例发病前2周有户外活动,15.8%病例有明确的蜱虫叮咬史。存活与死亡病例发病前家里有无老鼠有统计学意义（〖XC小五号.EPS;P〗=7.037,P=0.030）。99.2%的病例首发症状是发热,多数病例有乏力（81.2%）畏寒（61.7%）和食欲减退（55.6%）等非特异性症状,存活和死亡病例是否呕血有统计学差异（〖XC小五号.EPS;P〗=5.992,P=0.014）。从发病到确诊治疗M为5天,平均就医2.29次。市级及以上医院诊断率为86.3%。聚集性疫情的传播模式为“蜱叮咬-首发病例-体液、排泄物-续发病例”。69.8%的病例存在中等和严重的家庭负担,最严重的是经济负担（88.9%）。影响家庭负担的因素是婚姻状况和文化程度（P＜0.05）。结论 居住在丘陵/山区的高龄农民为SFTS的高危人群,季节发病明显。存活病例和死亡病例的主要差异在于呕血和发病前家有老鼠。县级及以下医院诊断能力低、就诊次数多,确诊时间延长从而加重家庭负担。应加强培训和宣传,早发现、早诊断、早治疗。     

Worse Breast Cancer Outcomes for Southern Nevadans,Filipina and Black Women

Breast cancer is the second deadliest cancer for women in the demographically unique mountainous west state of Nevada. This study aims to accurately characterize breast cancer survival among the diverse women of the flourishing Silver State. Nevada Central Cancer Registry data was linked with the National Death Index and the Social Security Administration Masterfile. Overall 5-year age-adjusted cause-specific survival, survival stratified by race/ethnicity, and stage-specific survival stratified by region of Nevada were calculated. Adjusted hazard ratios were computed with Cox proportional hazards regression. 11,111 cases of breast cancer were diagnosed from 2003 to 2010. Overall 5-year breast cancer survival in Nevada was 84.4 %, significantly lower than the US, at 89.2 %. Black and Filipina women had a higher risk of death than white women. Poor survival in the racially and ethnically diverse Las Vegas metropolitan area, with a large foreign-born population, drives Nevada’s low overall survival. System-wide changes are recommended to reduce the racial/ethnic disparities seen for black and Filipina women and improve outcomes for all.     

A comparison of the National Death Index and Social Security Administration databases to ascertain vital status

We compared vital status follow-up by the National Death Index and the Social Security Administration for a cohort of breast cancer patients. Only the National Death Index allowed follow-up for subjects with an unknown Social Security number. All of the deaths identified by the Social Security Administration were reported by the National Death Index. No subject reported to be alive by the Social Security Administration matched a National Death Index record. Subjects with inaccurate identifying information were more effectively followed up by the National Death Index. The National Death Index more accurately reported dates of death.     

Differential survival related to smoking among patients with renal cell carcinoma

We examined the relation between tobacco smoking and survival among renal cell carcinoma cases, using information from a population-based cancer registry. Current smokers were at increased risk of death compared with non-smokers (hazard ratio (HR) 1.7, 95% CI = 1.2-2.5). The association was strongest within 6 months of diagnosis (HR 2.5, 95% CI = 1.5-4.3). Most of the association was explained by stage at diagnosis, with current smokers more likely (OR 2.2, 95% CI = 1.4-3.5) to have distant disease. Case-control studies may be biased if cases who do not participate owing to short survival have different smoking histories than participating cases.     

Clinical and demographic factors and outcome of amyotrophic lateral sclerosis in relation to population ancestral origin

Background

To review how the phenotype and outcome of amyotrophic lateral sclerosis (ALS) change with variations in population ancestral origin (PAO). Knowledge of how PAO modifies ALS phenotype may provide important insight into the risk factors and pathogenic mechanisms of the disease.

Methods

We performed a systematic review and meta-analysis of the literature concerning differences in phenotype and outcome of ALS that relate to PAO.

Results

A review of 3111 records identified 78 population-based studies. The 40 that were included covered 40 geographical areas in 10 subcontinents. Around 12,700 ALS cases were considered. The results highlight the phenotypic heterogeneity of ALS at time of onset [age, sex ratio (SR), bulbar onset], age at diagnosis, occurrence of comorbidities in the first year after diagnosis, and outcome (survival). Subcontinent is a major explanatory factor for the variability of the ALS phenotype in population-based studies. Some markers of ALS phenotype were homogeneously distributed in western countries (SR, mean age at onset/diagnosis) but their distributions in other subcontinents were remarkably different. Other markers presented variations in European subcontinents (familial ALS, bulbar onset) and in other continents. As a consequence, ALS outcome strongly varied, with a median survival time from onset ranging from 24 months (Northern Europe) to 48 months (Central Asia).

Discussion

This review sets the scene for a collaborative study involving a wide international consortium to investigate, using a standard methodology, the link between ancestry, environment, and ALS phenotype.

     

Fatal asthma from powdering shark cartilage and review of fatal occupational asthma literature

BACKGROUND: Work-related asthma (WRA) is the most common work-associated respiratory disease in developed countries. METHOD: We report shark cartilage dust as a new potential cause of occupational asthma (OA) in the context of other fatal OA case reports. RESULTS: A 38-year-old white male worked for 8 years in a facility which primarily granulated and powdered various plastics. Sixteen months prior to his death, the plant began grinding shark cartilage. After 10 months of exposure, he reported chest symptoms at work in association with exposure to shark cartilage dust and a physician diagnosed asthma. Six months later, he complained of shortness of breath at work and died from autopsy-confirmed asthma. The latency from onset of exposure to symptoms and from symptom onset to death was shorter than 10 previously reported OA fatalities. CONCLUSION: Recognition of occupational causes and triggers of asthma and removal of affected individuals from these exposures is critical and can prevent progression to irreversible or even fatal asthma.